CD_(56)^+细胞源γ干扰素的表达与宫颈癌患者预后的关系研究

Relationship between CD_(56)^+-derived IFN-γ Expression and the Prognosis in Cervical Cancer

目的探讨CD_(56)^+细胞源γ干扰素(IFN-γ)的表达与宫颈癌患者预后的关系。方法选取2008年2月—2011年11月在唐山市工人医院活检或妇产科手术切除的宫颈炎、宫颈癌前病变及宫颈癌标本共计121例,其中慢性宫颈炎患者25例(对照组)、宫颈上皮内瘤变(CIN)Ⅰ级患者11例(CINⅠ组)、CINⅡ/Ⅲ级患者45例(CINⅡ/Ⅲ组),宫颈鳞癌(SCC)患者40例(SCC组)。采用免疫双荧光共定位法检测不同病理宫颈组织中CD_(56)^+细胞百分比和CD_(56)^+IFN-γ^+细胞百分比,检测人乳头瘤病毒(HPV)16、18型和其他12种高危型阳性率,实时荧光反转录聚合酶链式反应(qRT-PCR)法测定不同病理宫颈组织中IFN-γmRNA的表达。根据SCC组CD_(56)^+IFN-γ^+细胞百分比平均数分为CD_(56)^+IFN-γ^+高表达和CD_(56)^+IFN-γ^+低表达。对40例SCC组患者进行随访,单因素生存分析采用Kaplan-Meier绘制生存曲线,比较采用Log-rank检验,多因素生存分析采用Cox比例风险回归模型。结果 4组宫颈组织中CD_(56)^+细胞百分比和CD_(56)^+IFN-γ^+细胞百分比比较,差异均有统计学意义(P<0.05);其中CINⅠ组宫颈组织中CD_(56)^+细胞百分比较对照组升高(P<0.05);CINⅡ/Ⅲ组和SCC组宫颈组织中CD_(56)^+细胞百分比较对照组和CINⅠ组升高,CD_(56)^+IFN-γ^+细胞百分比较对照组和CINⅠ组降低(P<0.05);SCC组宫颈组织中CD_(56)^+细胞百分比和CD_(56)^+IFN-γ^+细胞百分比较CINⅡ/Ⅲ组降低(P<0.05)。4组HPV16阳性率比较,差异有统计学意义(P<0.05);4组HPV18、其他12种高危型阳性率比较,差异均无统计学意义(P>0.05)。对照组HPV16阳性者IFN-γmRNA表达低于HPV16阴性者(P<0.05);CINⅠ组HPV16阳性与阴性者IFN-γmRNA表达水平比较,差异无统计学意义(P>0.05);CINⅡ/Ⅲ和SCC组HPV16阳性者IFN-γmRNA表达高于HPV16阴性者(P<0.05)。不同淋巴结转移、FIGO分期SCC组患者宫颈组织中CD_(56)^+IFN-γ^+表达比较,差异均有统计学意义(P<0.05)。随访5年,40例SCC组患者,死亡11例(27.5%),生存29例(72.5%)。SCC组患者宫颈组织中CD_(56)^+IFN-γ^+高表达者生存率高于CD_(56)^+IFN-γ^+低表达者(92.86%与61.54%,χ2=4.405,P=0.036)。Cox比例风险回归分析结果显示,SCC组患者宫颈组织中CD_(56)^+IFN-γ^+表达与预后相关[HR=2.592,95%CI(1.171,4.013),P<0.05]。结论 CD_(56)^+细胞表达水平随宫颈病变进展而升高,CD_(56)^+IFN-γ^+表达却呈下降趋势,其与宫颈癌患者预后相关。

Objective To investigate the relationship between CD56^＋derived IFN-γ expression and the prognosis in patients with cervical cancer. Methods The enrolled participants were 121 patients with cervicitis, cervical precancerous lesions or cervical cancer confirmed by colposcopy biopsy or gynecological surgery in Tangshan Workers＇ Hospital from February2008 to November 2011,including 25 with chronic cervicitis（ control group）,11 with cervical intraepithelial neoplasia（ CIN）grade Ⅰ（ CIN Ⅰ group）,45 with CIN grade Ⅱ/Ⅲ（ CIN Ⅱ/Ⅲ group）,and 40 with squamous carcinoma of the cervix（ SCC）（ SCC group）. We used double-immunofluorescent staining to quantify CD56^＋（ NK cell specific marker） and CD56^＋IFN-γ~＋cells in the cervical tissues. The prevalence of HPV16 infection,HPV18 infection and infection with other 12 high-risk types of HPV in the cervical tissues were detected pathologically. Expression of IFN-γ mRNA in the above cervical tissues was measured by qRT-PCR. The SCC group was divided into high-level expression and low-level expression based on the mean value of percentage of CD56^＋IFN-γ~＋cells in the SCC group. All the patients in the SCC group were followed up. Univariate analysis of the survival rate was based on the Kaplan-Meier survival curve, and Log-rank test was used to compare the survival distributions. Multivariate analysis of the survival rate was performed by using the Cox＇ s proportional hazards models. Results The percentage of CD56^＋cells and CD56^＋IFN-γ~＋cells differed significantly among the 4 groups（ P〈0.05）. Compared with the control group, the percentage of CD56^＋cells in cervical tissues of CIN Ⅰ group was significantly increased（ P〈0.05）.Compared with the control and CIN Ⅰ group,the percentage of CD56^＋cells increased while that of CD56^＋IFN-γ~＋cells decreased significantly in cervical tissues of CIN Ⅱ/Ⅲ and SCC group（ P〈0.05）. Compared with CIN Ⅱ/Ⅲ group, both the percentages of CD56^＋cells and CD56^＋IFN-γ~＋cells decreased significantly in the cervical tissues of SCC group（ P〈0.05）. The prevalence of HPV16 infection in the cervical tissues differed obviously among the 4 groups（ P〈0.05）,but that of HPV18 infection and other 12 high-risk types of HPV infection did not（ P〈0.05）. Lower expression of IFN-γ mRNA was found in those with HPV16 infection than those without in the control group（ P〈0.05）. The expression of IFN-γ mRNA was not associated with HPV16 infection in patients in the CINⅠ group（ P〈0.05）. Higher expression of IFN-γ mRNA was found in those with HPV16 infection than those without in both the CINⅡ/Ⅲ group and SCC group（ P〈0.05）. Clinical parameters of lymph node metastasis and FIGO staging were associated with the CD56^＋IFN-γ~＋expression in SCC group（ P〈0.05）. During the follow-up period,11（ 27. 5%） of the 40 SCC cases died, the other 29（ 72. 5%） survived. Patients in high-level expression of CD56^＋IFN-γ~＋ had higher survival rate than those in the low-level expression of CD56^＋IFN-γ~＋（ 92. 86%vs. 61. 54%,χ~2= 4. 405,P = 0. 036）. The Cox regression analysis showed that,expression of CD56^＋IFN-γ~＋ was associated with the prognosis of patients in SCC group [HR = 2. 592,95% CI（ 1. 171,4. 013）,P〈0.05]. Conclusion The expression of CD56^＋cells significantly increase with the progression of cervical lesions,but the expression of CD56^＋IFN-γ~＋ significantly decline,which may be associated with the prognosis in SCC patients.